Pharmacokinetic Study of Sub-q and IV Treprostinil in Kids With Pulmonary Arterial Hypertension (PAH)

NCT02318186 | Completed DMC

• 1 other identifier: UT PK Treprostinil
• Study Type: observational
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Abstract This is a multi-center, open-label pharmacokinetic (PK) study examining the relationship between the steady-state plasma concentration and dose of treprostinil delivered intravenously or subcutaneously in children with pulmonary arterial hypertension (PAH). Subjects will be divided into 5 cohorts by age. A blood sample will be obtained from each subject at steady state. Additional blood samples will be obtained from a small subset of subjects with a 15% increase or with at least a 15ng/kg/min increase in dose from steady state. Samples will be sent to a pharmacokinetic laboratory for analysis. Linear regression analysis will be used to determine the relationship between the steady state plasma concentration and drug dose. A power model will be used to assess dose proportionality.

Conditions

Pulmonary Arterial Hypertension

Keywords

pharmacokinetic analysis; remodulin; trepostinil; pulmonary arterial hypertension

Outcome Measures

Primary Outcomes (1)

• To determine the relationship between steady-state plasma concentration and dose of treprostinil within each age cohort and among age cohorts.

  A blood sample will be obtained from each subject at steady state. Additional blood samples will be obtained from a small subset of subjects with a 15% increase or with at least a 15ng/kg/min increase in dose from steady state.

  at least 48 hours after most-recent titration

Secondary Outcomes (1)

• To correlate PK level of treprostinil with the presence or absence of side effects

  At time of blood draw

Study Arms (5)

0 months - 1 year

11-16 years

7-11 years

4-6 years

1-3 years

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Target enrollment for this study is a total of 50 pediatric patients among all participating sites with a goal of 65 total blood samples. Cohorts will be: 0-12 months; 1-3 years; 4-6 years; 7-11 years; 11-16 years. Each cohort will have 10 patients with 5 patients on a dose ≤ 50ng/kg/min and 5 patients on a dose ≥51-120ng/kg/min.

You may qualify if:

• Patients must be on continuous intravenous or subcutaneous treprostinil for the treatment of pulmonary arterial hypertension, defined as mean pulmonary artery pressure \>25mmHg at rest with a PVRi \> 3 Wood units.
• Patients must be between the ages of 0 to 16 years at the time of study enrollment.
• Written informed consent and assent, when applicable, must be completed.

You may not qualify if:

• Patients with severe liver or renal diseases.
• Female patients who may be pregnant or breastfeeding
• Written informed consent and assent not completed due to patient and/or parent or legal guardian unwilling to participate.
• Patients on concomitant use of a CYP2C inhibitor or inducer.

Sponsors & Collaborators

• Jeffrey A. Feinstein: lead
• United Therapeutics: collaborator
• Seattle Children's Hospital: collaborator
• University of Colorado, Denver: collaborator
• Children's Hospital of Philadelphia: collaborator

Study Sites (1)

Lucille Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

Related Publications (3)

• Ivy DD, Claussen L, Doran A. Transition of stable pediatric patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. Am J Cardiol. 2007 Mar 1;99(5):696-8. doi: 10.1016/j.amjcard.2006.09.119. Epub 2007 Jan 10.

  PMID: 17317374 BACKGROUND

• Levy M, Celermajer DS, Bourges-Petit E, Del Cerro MJ, Bajolle F, Bonnet D. Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. J Pediatr. 2011 Apr;158(4):584-8. doi: 10.1016/j.jpeds.2010.09.025. Epub 2010 Oct 30.

  PMID: 21035821 BACKGROUND

• McSwain CS, Benza R, Shapiro S, Hill N, Schilz R, Elliott CG, Zwicke DL, Oudiz RJ, Staszewski JP, Arneson CP, Wade M, Zaccardelli D, McLaughlin V. Dose proportionality of treprostinil sodium administered by continuous subcutaneous and intravenous infusion. J Clin Pharmacol. 2008 Jan;48(1):19-25. doi: 10.1177/0091270007309708.

  PMID: 18094217 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

2 mL blood sample in K3-EDTA tube and immediately place on ice; Place plasma into 2 aliquots; Freeze at -20 degrees or lower. Store until batch is complete; Batch ship all samples on dry ice to pharmacokinetic analytical laboratory

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jeffrey Feinstein, MD, MPH

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Vera Moulton Wall Center for Pulmonary Vascular Disease

Study Record Dates

• First Submitted: January 9, 2014
• First Posted: December 17, 2014
• Study Start: October 1, 2013
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: October 5, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)